Hypersensitivity to acute ANG II in female growth-restricted offspring is exacerbated by ovariectomy

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2011-10, Vol.301 (4), p.R1199-R1205
• Main Authors: Ojeda, Norma B, Intapad, Suttira, Royals, Thomas P, Black, Joshua T, Dasinger, John Henry, Tull, F Lee, Alexander, Barbara T
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Angiotensin II - pharmacology; Animals; Animals, Newborn - growth & development; Animals, Newborn - physiology; Antihypertensive Agents - pharmacology; Blood Pressure - drug effects; Blood Pressure - physiology; Body Weight - physiology; Enalapril - pharmacology; Female; Fetal Growth Retardation - physiopathology; Gender; Hormones; Hypertension; Male; Models, Animal; Ovariectomy; Phenylephrine - pharmacology; Pregnancy; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Sex Characteristics; Vasoconstrictor Agents - pharmacology
• ISSN: 0363-6119; 1522-1490; 1522-1490
• DOI: 10.1152/ajpregu.00219.2011

Female growth-restricted offspring are normotensive in adulthood. However, ovariectomy induces a marked increase in mean arterial pressure (MAP) that is abolished by renin angiotensin system (RAS) blockade, suggesting RAS involvement in the etiology of hypertension induced by ovariectomy in adult female growth-restricted offspring. Blockade of the RAS also abolishes hypertension in adult male growth-restricted offspring. Moreover, sensitivity to acute ANG II is enhanced in male growth-restricted offspring. Thus, we hypothesized that an enhanced sensitivity to acute ANG II may contribute to hypertension induced by ovariectomy in female growth-restricted offspring. Female offspring were subjected to ovariectomy (OVX) or sham ovariectomy (intact) at 10 wk of age. Cardio-renal hemodynamic parameters were determined before and after an acute infusion of ANG II (100 ng·kg(-1)·min(-1) for 30 min) at 16 wk of age in female offspring pretreated with enalapril (40 mg·kg(-1)·day(-1) for 7 days). Acute ANG II induced a significant increase in MAP in intact growth-restricted offspring (155 ± 2 mmHg, P < 0.05) relative to intact control (145 ± 4 mmHg). Ovariectomy augmented the pressor response to ANG II in growth-restricted offspring (163 ± 2 mmHg, P < 0.05), with no effect in control (142 ± 2 mmHg). Acute pressor responses to phenylephrine did not differ in growth-restricted offspring relative to control, intact, or ovariectomized. Furthermore, renal hemodynamic responses to acute ANG II were significantly enhanced only in ovariectomized female growth-restricted offspring. Thus, these data suggest that enhanced responsiveness to acute ANG II is programmed by intrauterine growth restriction and that sensitivity to acute ANG II is modulated by ovarian hormones in female growth-restricted offspring.